scholarly journals A Cyclic Peptide Mimicking the Third Intracellular Loop of the V2Vasopressin Receptor Inhibits Signaling through Its Interaction with Receptor Dimer and G Protein

2004 ◽  
Vol 279 (49) ◽  
pp. 50904-50914 ◽  
Author(s):  
Sébastien Granier ◽  
Sonia Terrillon ◽  
Robert Pascal ◽  
Hélène Déméné ◽  
Michel Bouvier ◽  
...  
Keyword(s):  
G Protein ◽  
Cyclic Peptide ◽  
Intracellular Loop ◽  
The Third ◽  
Third Intracellular Loop ◽  
Receptor Dimer

scholarly journals Mutational analysis of the mouse 5-HT7 receptor: importance of the third intracellular loop for receptor-G-protein interaction

FEBS Letters ◽  
1997 ◽  
Vol 412 (2) ◽  
pp. 321-324 ◽  
Author(s):  
Louis A Obosi ◽  
René Hen ◽  
David J Beadle ◽  
Isabel Bermudez ◽  
Linda A King
Keyword(s):  
G Protein ◽  
Protein Interaction ◽  
Mutational Analysis ◽  
Intracellular Loop ◽  
The Third ◽  
Third Intracellular Loop

scholarly journals Recycling ability of the mouse and the human neurotensin type 2 receptors depends on a single tyrosine residue

2002 ◽  
Vol 115 (1) ◽  
pp. 165-173
Author(s):  
Stéphane Martin ◽  
Jean-Pierre Vincent ◽  
Jean Mazella
Keyword(s):  
G Protein ◽  
Kinase Inhibitor ◽  
Site Directed Mutagenesis ◽  
Tyrosine Residue ◽  
Receptor Recycling ◽  
Intracellular Loop ◽  
Structural Element ◽  
The Third ◽  
Third Intracellular Loop ◽  
G Protein Coupled

Receptor recycling plays a key role in the modulation of cellular responses to extracellular signals. The purpose of this work was to identify residues in G-protein coupled neurotensin receptors that are directly involved in recycling. Both the high affinity receptor-1 (NTR1) and the levocabastine-sensitive NTR2 are internalized after neurotensin binding. Here, we show that only the mouse NTR2 recycled to the plasma membrane, whereas the rat NTR1 and the human NTR2 did not. Using site-directed mutagenesis, we demonstrate that tyrosine 237 in the third intracellular loop is crucial for recycling of the mouse NTR2. We show that the mouse NTR2 is phosphorylated on tyrosine residues by NT. This phosphorylation is essential for receptor recycling since the tyrosine kinase inhibitor genistein blocks this process. The absence of recycling observed with the human NTR2 could be completely explained by the presence of a cysteine instead of a tyrosine in position 237. Indeed, substitution of this cysteine by a tyrosine gave a mutant receptor that has acquired the ability to recycle to the cell surface after neurotensin-induced internalization. This work demonstrates that a single tyrosine residue in the third intracellular loop of a G-protein-coupled receptor is responsible for receptor phosphorylation and represents an essential structural element for receptor recycling.

scholarly journals Down-regulation of PAR1 activity with a pHLIP-based allosteric antagonist induces cancer cell death

2015 ◽  
Vol 472 (3) ◽  
pp. 287-295 ◽  
Author(s):  
Kelly E. Burns ◽  
Damien Thévenin
Keyword(s):  
Cell Death ◽  
Cancer Cells ◽  
G Protein ◽  
Cancer Cell ◽  
Intracellular Loop ◽  
The Third ◽  
Cancer Cell Death ◽  
Third Intracellular Loop ◽  
Ph Dependent ◽  
G Protein Coupled

A pH(Low) Insertion Peptide (pHLIP)-based construct derived from the third intracellular loop (i3) of a G protein-coupled receptor (GPCR) induces a concentration- and pH-dependent cytotoxicity in cancer cells by down-regulating receptor activity. This strategy allows for a more selective intracellular delivery than current approaches.

scholarly journals The role of the third intracellular loop of the neutrophil N-formyl peptide receptor in G protein coupling

1993 ◽  
Vol 294 (2) ◽  
pp. 581-587 ◽  
Author(s):  
E R Prossnitz ◽  
O Quehenberger ◽  
C G Cochrane ◽  
R D Ye
Keyword(s):  
Amino Acids ◽  
G Protein ◽  
Formyl Peptide Receptor ◽  
Wild Type ◽  
Intracellular Loop ◽  
G Protein Coupling ◽  
Protein Coupling ◽  
The Third ◽  
Third Intracellular Loop ◽  
Formyl Peptide

The G-protein-coupled N-formyl peptide receptor (FPR) contains one of the smallest known third intracellular loops of this class of receptors, consisting of only 15 amino acids. To study the role of this region of the receptor in G protein coupling and signal transduction, we generated a deletion mutant (D3i) in which 10 amino acids of the loop were removed, as well as a series of site-directed mutants containing substitutions of the charged and polar amino acids of this loop. The D3i mutant, expressed at normal levels on the cell surface, displayed a KD for labelled N-formyl-Met-Leu-Phe ([3H]FMLP) of 165 nM. This value compares with a KD for the wild-type FPR of 1.0 nM, or 20 nM in the presence of guanosine 5′-[gamma-thio]triphosphate, which uncouples G proteins from the receptor. These results indicate that D3i contains significant structural defects, beyond the disruption of G protein coupling, that affect ligand binding properties. Ten site-directed mutants generated in the third intracellular loop (T226A, K227E, H229A, K230Q, K235Q, S236A, S236A/S237G, R238G, R241E and S244A) displayed KD values between 0.5 and 1.0 nM, with expression levels between 22% (K227E) and 111% (H229A) of that of wild type receptor. The capacity of the mutants for signal transductions was determined by measuring intracellular Ca2+ mobilization. Eight of the ten mutants displayed EC50 values for FMLP of between 0.07 and 0.9 nM, as compared with 0.12 nM for the wild-type receptor. The two mutants K227E and R238G had EC50 values of 2.7 and 2.9 nM respectively. The increase in EC50 could be accounted for partially by the low levels of receptor expression. All ten mutants gave maximum levels of Ca2+ mobilization similar to that produced by the wild-type FPR. These results contradict the conclusions reached with other G-protein-coupled receptors and indicate that the third intracellular loop of the FPR does not have a critical role in the functional coupling of G proteins.

Spinophilin regulates Ca2+ signalling by binding the N-terminal domain of RGS2 and the third intracellular loop of G-protein-coupled receptors

2005 ◽  
Vol 7 (4) ◽  
pp. 405-411 ◽  
Author(s):  
Xinhua Wang ◽  
Weizhong Zeng ◽  
Abigail A. Soyombo ◽  
Wei Tang ◽  
Elliott M. Ross ◽  
...  
Keyword(s):  
G Protein ◽  
G Protein Coupled Receptors ◽  
Intracellular Loop ◽  
The Third ◽  
Terminal Domain ◽  
Third Intracellular Loop ◽  
G Protein Coupled
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